U.S. Pat. No. 5,100,889 to Misra et al discloses 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs which are thromboxane A.sub.2 (TXA.sub.2) receptor antagonists or combined thromboxane A.sub.2 receptor antagonist/thromboxane synthetase inhibitors useful, for example, in the treatment of thrombotic and/or vasospastic diseases, and have good duration of action. Examples of compounds disclosed in Misra et al have the structural formula I ##STR3## and including all stereoisomers thereof, wherein
m is 1, 2 or 3; n is 0, 1, 2, 3 or 4;
R.sup.1 is hydrogen, lower alkyl, aralkyl, aryl, cycloalkyl, cyclo-alkylalkyl, or amide ##STR4## wherein t is 1 to 12 and R.sub.a is lower alkyl, aryl, cycloalkyl, or cycloalkylalkyl);
R.sub.2 is hydrogen, lower alkyl, aryl, or aralkyl; or R.sup.1 and R.sup.2 together with the nitrogen to which they are linked may form a 5- to 8- membered ring.
Misra et al disclose that these compounds may be prepared from the oxazoline XV' ##STR5## which is made to undergo oxidation using manganese dioxide, or nickel peroxide, or preferably cupric bromide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to form the oxazole I. ##STR6##
The cupric bromide oxidation is carried out at a temperature of within the range of from about 20.degree. C. to about 70.degree. C., employing a molar ratio of cupric bromide to XV' of within the range of from about 2:1 to about 6:1 and a molar ratio of cupric bromide to DBU of within the range of from about 1:1 to about 1:3 in an inert solvent, preferably ethyl acetate/chloroform (1:1, v/v).
The so-formed oxazole may then be hydrolyzed by treatment with an aqueous solution of alkali metal base and then aqueous acid to form the corresponding acid.
In Example 1 Part O of Misra et al, the methyl ester of the final product is prepared together with the corresponding bromooxazole as a side product (6% yield).